Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm  

作　　者：Bo Chen Jiawen Teng Hongwei Liu Xu Pan Ya Zhou Shu Huang Mowen Lai Guohui Bian Bin Mao Wencui Sun Qiongxiu Zhou Shengyong Yang Tatsutoshi Nakahata Feng Ma 

机构地区：[1]Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China [2]State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610065, China [3]Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan [4]State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin 300020, China

出　　处：《Journal of Molecular Cell Biology》2017年第4期262-273,共12页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Program on Key Basic Research Project of China （973 Program; 2015CB964902）, the National Natural Science Foundation of China （NSFC; H81170466 and H81370597）, and the CAMS Initiatives for Innovative Medicine （2016-12M-1-018） awarded to F.M.

摘　　要：RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.

关 键 词：RUNX1/AML1 HEMATOPOIESIS hemogenic endothelium MESODERM TGF-β signaling pathway HESC inducible expressionsystem 

分 类 号：Q813[生物学—生物工程] S896.3[农业科学—特种经济动物饲养]